ArticleJournal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research2011
Tristetraprolin regulates interleukin-6 expression through p38 MAPK-dependent affinity changes with mRNA 3' untranslated region.
Article in Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 98 citations in OpenAlex.
- Selective decay of interferon mRNAs controls antiviral immunity and innate memory.Molecular cell · 2026Article
- LPS-Induced TNF-α and IL-1 Signaling in Periodontitis: Molecular Mechanisms and Therapeutic Opportunities.Current issues in molecular biology · 2026Review
- ZFP36 Family Proteins as Critical Regulators of Inflammation, Immune Cell Development, and Antiviral Responses.Vaccines · 2026Review
- The ZFP36 Family as Post-Transcriptional Regulators in Physiology and Disease.International journal of molecular sciences · 2026Review
- The ZFP36 Family as a Post-Transcriptional Immune Checkpoint in Immunity and Disease: Molecular Mechanisms and Functional Implications.Biomolecules · 2026Review
- RNA-binding proteins in aging and age-related diseases: roles, mechanisms, and a large language model analysis.Biogerontology · 2026Review
- Tristetraprolin protects against ozone-induced acute lung injury and inflammation in mice.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- The RNA-Binding Protein KSRP Is a Negative Regulator of Innate Immunity.Biomolecules · 2025Review
- Review of roles of RNA-binding proteins on NAFLD and the related pharmaceutical measures.Biomolecules & biomedicine · 2025Review
- Deletion of smooth muscle ZFP36 promotes neointimal hyperplasia in mice.Acta pharmacologica Sinica · 2025Article
- Restraint of inflammasome-driven cytokine responses through the mRNA stability protein TTP.Cell reports · 2025Article
- ZFP36L1 and ZFP36L2 reduce cyclin D1 expression by decreasing expression of E2F1 and long 3'UTR isoform of CCND1 transcripts.Molecular and cellular biochemistry · 2025Article
- Regulation of inflammatory diseases via the control of mRNA decay.Inflammation and regeneration · 2024Review
- Article
- Inflammation as a driver of hematological malignancies.Frontiers in oncology · 2024Review
- Tristetraprolin regulates the skeletal phenotype and osteoclastogenic potential through monocytic myeloid-derived suppressor cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Synergistic roles of tristetraprolin family members in myeloid cells in the control of inflammation.Life science alliance · 2024Article
- Interleukin-6 in Traumatic Brain Injury: A Janus-Faced Player in Damage and Repair.Journal of neurotrauma · 2023Review
- Important Cells and Factors from Tumor Microenvironment Participated in Perineural Invasion.Cancers · 2023Review
- Clinical implications of tristetraprolin (TTP) modulation in the treatment of inflammatory diseases.Pharmacology & therapeutics · 2022Review
12 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Tristetraprolin (TTP) is a well-characterized, zinc finger-containing, RNA-binding protein. TTP targets tumor necrosis factor α for degradation via the 3' untranslated region (3'UTR). Although AU-rich elements (AREs) in the 3'UTR of interleukin-6 (IL-6) mRNA dictate mRNA degradation, the role of TTP in the post-transcriptional regulation of IL-6 gene expression is unclear. Here we used TTP-deficient mice to test the hypothesis that IL-6 expression is influenced by TTP. Genetic and siRNA-mediated knockdown of TTP resulted in increased IL-6 production and overexpression of TTP had the reverse effect. IL-6 and tumor necrosis factor α production were elevated after injection of IL-1β in TTP-deficient mice. Further, embryonic fibroblasts from these mice (mouse embryonic fibroblasts) exhibited greater IL-6 mRNA expression and longer half-life than wild-type mouse embryonic fibroblasts. Overexpression of TTP reduced IL-6 3'UTR luciferase reporter activity in an ARE-dependent manner. Proximal and distal regions of the 3'UTR acted synergistically to produce the full repression of TTP. Mutation-based luciferase assays show that ARE2, ARE3, and ARE4 are required for TTP-mediated repression. The constitutively activated p38-MK2 pathway abrogated TTP-mediated repression of IL-6 3'UTR reporter activity. RNA immunoprecipitation assay indicated that the deficiency of p38α resulted in the increased affinity of TTP to IL-6 mRNA. Taken together, we propose that TTP downregulates IL-6 gene expression at the post-transcriptional level by targeting ARE elements in the 3'UTR region.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.